title: Impact of MET expression on outcome in BRAF(V600E/K) advanced melanoma.
abstract: OBJECTIVE
  Preclinical data suggest that signalling through the HGF-MET pathway may confer resistance to BRAF inhibition in BRAF(V600E/K) melanoma. Therefore, blockade of HGF-MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAF(V600E/K) melanoma. The aim of this study was to investigate the clinical relevance of these observations by evaluating the survival impact of MET expression in patients with BRAF(V600E/K) advanced melanoma treated with vemurafenib.
  
  
  RESULTS
  Formalin-fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 (n = 59) and BRIM3 (n = 150) trials of vemurafenib in advanced BRAF(V600E/K) melanoma. Immunohistochemistry for MET (SP44 rabbit monoclonal antibody) was performed with a highly validated assay and clinically validated scoring system. Pretreatment MET expression was frequent at the ≥1 + cutoff (BRIM3, 31%; BRIM2, 49%), but relatively infrequent at the ≥2 + cutoff (BRIM3, 9%; BRIM2, 19%). Retrospective subset analyses showed that, irrespective of the cutoff used or the treatment arm, MET expression did not show prognostic significance, in terms of objective response rate, progression-free survival, or overall survival.
  
  
  CONCLUSIONS
  MET is expressed in a proportion of BRAF(V600E/K) advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib-treated melanoma.
authors.affiliation: Product Development-Oncology, Genentech Inc., South San Francisco, CA, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Jubb
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yan
authors.forename: Sandra
authors.initials: S
authors.lastname: Rost
authors.forename: Sherry
authors.initials: S
authors.lastname: Zhao
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011817:Rabbits; D012189:Retrospective Studies; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D007211:Indoles; D050505:Mutant Proteins; D013449:Sulfonamides; D000077484:Vemurafenib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; HGF; MET; SP44; melanoma